PDF(Pubmed)
Abstract：
UNASSIGNED: Myeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions.
UNASSIGNED: MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.
UNASSIGNED: Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.
UNASSIGNED: In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.
UNASSIGNED: MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.
UNASSIGNED: Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.
UNASSIGNED: In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.
摘要：
■骨髓增殖性肿瘤（MPN）是一组异质性的血液恶性肿瘤，包括真性红细胞增多症（PV），原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）。JAK2V617F是所有三个实体中最常见的驱动突变，但在PMF和ET中CALR和MPL的突变也很常见。无论MPN的亚型如何，在其他基因中看到的突变通常也是相同的。这项研究的目的是分析基于人群的MPN队列中具有预后价值的遗传变异，可以指导临床决策。
■在2008-2013年间诊断的来自瑞典西部的MPN患者（n=248）进行了与骨髓恶性肿瘤相关的54个基因的突变筛查。
■SRSF2和U2AF1基因的突变与总体生存率降低显著相关，但与血管事件风险增加无关。在诊断之前或之后。相反，这些基因的突变显示与疾病转化有关。等位基因频率接近50％的几种复发基因变体被证实是种系。然而,没有发现这些变体具有较早的MPN发作。
■总而言之，我们发现基因突变是MPN存活受损的独立标志物.这表明需要对MPN患者进行更个性化的评估和治疗，并在诊断时进行更广泛的基因突变筛查。这可以确保早期识别具有高风险突变的患者。此外,在这项研究中,几种遗传变异也被鉴定为种系,但没有明显的临床相关性.为了避免非信息遗传变异的结论，应考虑在诊断时同时分析患者的正常细胞DNA.
■在2008-2013年间诊断的来自瑞典西部的MPN患者（n=248）进行了与骨髓恶性肿瘤相关的54个基因的突变筛查。
■SRSF2和U2AF1基因的突变与总体生存率降低显著相关，但与血管事件风险增加无关。在诊断之前或之后。相反，这些基因的突变显示与疾病转化有关。等位基因频率接近50％的几种复发基因变体被证实是种系。然而,没有发现这些变体具有较早的MPN发作。
■总而言之，我们发现基因突变是MPN存活受损的独立标志物.这表明需要对MPN患者进行更个性化的评估和治疗，并在诊断时进行更广泛的基因突变筛查。这可以确保早期识别具有高风险突变的患者。此外,在这项研究中,几种遗传变异也被鉴定为种系,但没有明显的临床相关性.为了避免非信息遗传变异的结论，应考虑在诊断时同时分析患者的正常细胞DNA.
